Lifestyle-related diseases such as diabetes mellitus, hyperlipemia, hypertension, and ischemic heart disease represent the major cause of oppressing the medical finances in advanced countries, including Japan. Modern people are liable to overeating and underexcersise; as a result, excess energy is accumulated in adipose tissue as neutral fats, which in turn causes obesity.
In recent years, it has been shown that various physiologically active proteins secreted from adipose tissue (generically referred to as adipocytokines) mediate metabolic regulation and insulin resistance, and their application to the treatment of lifestyle-related diseases has been attempted. For example, adiponectin was identified as an adipocytokine that occurs at high concentrations in blood, the secretion of which decreases with the increase in visceral fat (non-patent document 1), and it has been suggested that the decrease in the secretion of this hormone and the reduction in insulin action may be closely associated with each other (non-patent document 2). On the other hand, resistin was identified as a hormone secreted from adipocytes, which decreases the insulin action in adipose tissue, skeletal muscles, liver and the like (non-patent document 3), and is drawing attention as an adipocytokine closely associated with the onset of insulin resistance. Also, it has been shown that if fat accumulation occurs, plasminogen activator inhibitor-1 (PAI-1) is expressed remarkably in visceral fat and its blood concentration increases, which can be a cause of vascular complications (non-patent document 4).
Fat accumulation in obesity also occurs in the liver, muscles, pancreas, vascular walls and the like, and causes metabolic abnormalities in these organs, resulting in the onset of insulin resistance, diabetes mellitus, hyperlipemia, hypertension and the like. These organs are considered to be mutually associated via endocrine factors to achieve complex and sophisticated metabolic regulation. It is postulated, therefore, that endocrine factors acting like adipocytokines are also produced and secreted from muscles, liver, small intestine, blood vessels and the like, but to date there have been almost no reports on such factors.    Non-patent document 1: Arita et al., “Biochemical and Biophysical Research Communication”, (USA), 1999, Vol. 257, pp. 79-83    Non-patent document 2: Hotta et al., “Diabetes,” (USA), 2001, Vol. 50, pp. 1126-1133    Non-patent document 3: Steppan et al., “Nature,” (UK), 2001, Vol. 409, pp. 307-312    Non-patent document 4: Shimomura et al., “Nature Medicine”, (USA), 1996, Vol. 2, pp. 800-803